Conversion of epidermal growth factor receptor 2 and hormone receptor expression in breast cancer metastases to the brain

Abstract

IntroductionWe investigated the status of estrogen receptor alpha (ERα), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER2) in primary tumor and in the corresponding brain metastases in a consecutive series of breast cancer patients. Additionally, we studied factors potentially influencing conversion and evaluated its association with survival.MethodsThe study group included 120 breast cancer patients. ERα, PR, and HER2 status in primary tumors and in matched brain metastases was determined centrally by immunohistochemistry and/or fluorescence in situ hybridization.ResultsUsing the Allred score of ≥ 3 as a threshold, conversion of ERα and PR in brain metastases occurred in 29% of cases for both receptors, mostly from positive to negative. Conversion of HER2 occurred in 14% of patients and was more balanced either way. Time to brain relapse and the use of chemotherapy or trastuzumab did not influence conversion, whereas endocrine therapy induced conversion of ERα (P = 0.021) and PR (P = 0.001), mainly towards their loss. Receptor conversion had no significant impact on survival.ConclusionsReceptor conversion, particularly loss of hormone receptors, is a common event in brain metastases from breast cancer, and endocrine therapy may increase its incidence. Receptor conversion does not significantly affect survival.

Breast cancer during follow-up and progression – A population based cohort on new cancers and changed biology

“…This finding is in line with previous studies demonstrating that neoadjuvant therapy such as chemotherapy, trastuzumab and endocrine therapy seems to affect the receptor status of the primary tumour [11,12]. In addition, loss of ER has been observed following treatment with endocrine therapy in the advanced settings [13]. Also in a study from Niikura et al, included patients with paired primary-and metastatic breast cancer tumours, loss of HER2 overexpression was significantly higher among those who received chemotherapy compared to the patients who did not (P = 0.022) irrespectively of whether the patients received trastuzumab therapy [1].…”

“…Additionally, adjuvant therapies may also influence a clonal selection resulting in different phenotype of the metastatic-, and primary tumour cell [1,3,13,30]. Indeed, such an association between adjuvant therapy and hormonal receptor status was seen in the present paper, as well as in a previous report by our group [3].…”

Evaluation of the pharmacological activities of RAD1901, a selective estrogen receptor degrader

“…However, few treatments can access the brain, one of three most frequent sites of metastasis for breast cancer, leaving targeted or whole brain radiation as the standard of care for patients diagnosed by BCBM (Freedman and Anders 2012). Importantly, in the majority of BCBM occurring in patients diagnosed with ESR1-positive breast tumors, ESR1 expression is retained, and the high expression of aromatase in the brain suggests that the disruption of ESR1 signaling may be beneficial in this setting (Duchnowska, et al 2012). Indeed, anecdotal evidence would support a role for ESR1 as a therapeutic target in BCBM (Madhup, et al 2006; Pors, et al 1991; Salvati, et al 1993).…”

Intérêt de la documentation biologique de la maladie métastatique cérébrale dans le cancer du sein : à propos d’un cas

“…Environ 10 à 16 % des patients atteints de cancer du sein métastatique présentent une localisation secondaire cérébrale [1]. L'incidence de l'atteinte cérébrale chez les patients atteints de cancers est en augmentation, à la fois grâce aux techniques d'imagerie, plus sensibles et plus fréquemment réalisées mais également grâce aux progrès des traitements systémiques [2] responsables d'une augmentation de la survie globale dans cette population.…”

“…Par ailleurs, l'avènement des thérapies ciblées en oncologie, associées ou non à un traitement cytotoxique a permis une amélioration significative de la survie des patients atteints de cancers sein [2,6].…”